Adenocarcinoma of the endometrium occurs principally in postmenopausal women. Numerous studies have been published both for and against the association of abnormal estrogen metabolism and the development of this tumor. In postmenopausal women, most if not all, estrogen production comes from the extraglandular conversion of androgens and not from direct secretion by either the ovaries or adrenals. In selected postmenopausal women who are obese and have hyperplasia or carcinoma of the endometrium, there is increased peripheral conversion of androstenedione to estrone resulting in increased estrone production. In preliminary studies the principal investigator team of the proposal has measured serum levels of estradiol, estrone, testosterone and androstenedione and found no difference between the circulating levels of any of these hormones in 16 unselected postmenopausal women with endometrial cancer and in 10 age and weight matched controls. Positive correlations were noted between both estradiol and estrone levels and the body weight of the endometrial cancer patients. In addition, data were obtained that showed the postmenopausal ovary continued to secrete substantial amounts of both testosterone and androstenedione in women with and without endometrial cancer. Based on these previous findings, we now propose to evaluate with a more comprehensive protocol the source and metabolism of estrogens and androgens in postmenopausal women with and without endometrial cancer. This will be done by 1) measuring the metabolic clearance rates, production rates, androgen to estrogen conversion rates, as well as the serum concentration of estradiol, estrone, testosterone, and androstenedione in unselected postmenopausal women with endometrial cancer and in weight and age matched controls. 2) Determining the effect of bilateral oophorectomy and estrogen and androgen metabolism in the same group of subjects. 3) Correlating the gross and histological appearance of each tumor with the endocrine results. The ultimate goal of these studies is to determine conclusively if abnormal estrogen metabolism exists in any, some, or all postmenopausal patients with this cancer.